General Information:

Id: 6,771
Diseases: Cardiovascular disease
Homo sapiens
BTO:0001949 HUVEC cell or left main coronary arteries from patients
article
Reference: [PMID: 26517696]

Interaction Information:

Comment The extent of coronary atherosclerosis in a patient set strongly correlated with loss of endothelial FGFR1 expression, activation of endothelial TGF-beta signaling, and the extent of EndMT, as shown in left coronary arteries.
Formal Description
Interaction-ID: 65763

decreases_expression of

gene/protein

FGFR1

in left main coronary arteries
Drugbank entries Show/Hide entries for FGFR1
Comment The extent of coronary atherosclerosis in a patient set strongly correlated with loss of endothelial FGFR1 expression, activation of endothelial TGF-beta signaling, and the extent of EndMT, as shown in left coronary arteries.
Formal Description
Interaction-ID: 65769

increases_activity of

in left main coronary arteries
Comment The extent of coronary atherosclerosis in a patient set strongly correlated with loss of endothelial FGFR1 expression, activation of endothelial TGF-beta signaling, and the extent of EndMT, as shown in left coronary arteries.
Formal Description
Interaction-ID: 65770

increases_activity of

process

endothelial to mesenchymal transition

in left main coronary arteries
Comment While 81% of the luminal endothelium in patients with no/mild CAD (coronary artery disease) demonstrated expression of FGFR1, this was reduced to 47.6% of the luminal endothelium in patients with moderate CAD and 11.1% in patients with severe CAD. In the same samples, p-SMAD2, a marker of activated TGF-beta signaling, progressively increased with disease severity.
Formal Description
Interaction-ID: 65772

increases_activity of

gene/protein

SMAD2

in left main coronary arteries
Drugbank entries Show/Hide entries for SMAD2
Comment NOTCH3 and SM22-alpha (TAGLN) are markers of EndMT (endothelial to mesenchymal transition). While essentially no luminal coronary ECs (endothelial cells) expressed these proteins in the absence of disease, their prevalence increased significantly with disease severity, with virtually all ECs in the left main arteries from patients with severe CAD (coronary artery disease) showing strong staining.
Formal Description
Interaction-ID: 65774

process

endothelial to mesenchymal transition

increases_quantity of

gene/protein

NOTCH3

in left main coronary arteries
Comment NOTCH3 and SM22-alpha (TAGLN) are markers of EndMT (endothelial to mesenchymal transition). While essentially no luminal coronary ECs (endothelial cells) expressed these proteins in the absence of disease, their prevalence increased significantly with disease severity, with virtually all ECs in the left main arteries from patients with severe CAD (coronary artery disease) showing strong staining.
Formal Description
Interaction-ID: 65775

process

endothelial to mesenchymal transition

increases_quantity of

gene/protein

TAGLN

in left main coronary arteries
Comment The extracellular matrix proteins collagen and fibronectin are well-recognized markers of epithelial-to-mesenchymal transition. There was a strong linear relationship between increasing endothelial expression of collagen and fibronectin and disease severity.
Formal Description
Interaction-ID: 65776

process

endothelial to mesenchymal transition

increases_quantity of

gene/protein

COL1A1

in left main coronary arteries
Drugbank entries Show/Hide entries for COL1A1
Comment The extracellular matrix proteins collagen and fibronectin are well-recognized markers of epithelial-to-mesenchymal transition. There was a strong linear relationship between increasing endothelial expression of collagen and fibronectin and disease severity.
Formal Description
Interaction-ID: 65777

process

endothelial to mesenchymal transition

increases_quantity of

gene/protein

FN1

in left main coronary arteries
Comment HUVECs (human umbilical vein endothelial cells), treated with increasing concentrations of the cytokines IFN-gamma, TNF-alpha, or IL-1-beta showed a decrease in FGFR1 expression and an increase in EndMT markers. The reduction in FGFR1 expression was most pronounced when IFN-gamma, TNF-alpha, and IL-1-beta were used together.
Formal Description
Interaction-ID: 65793

gene/protein

Proinflammatory cytokine

decreases_expression of

gene/protein

FGFR1

in HUVEC cells
Drugbank entries Show/Hide entries for FGFR1
Comment HUVECs (human umbilical vein endothelial cells), treated with increasing concentrations of the cytokines IFN-gamma, TNF-alpha, or IL-1-beta showed a decrease in FGFR1 expression and an increase in EndMT markers. The reduction in FGFR1 expression was most pronounced when IFN-gamma, TNF-alpha, and IL-1-beta were used together.
Formal Description
Interaction-ID: 65795

gene/protein

Proinflammatory cytokine

increases_activity of

process

endothelial to mesenchymal transition

in HUVEC cells
Comment Induction of EndMT (endothelial to mesenchymal transition) by inflammatory cytokines in ECs (endothelial cells) in vitro resulted in an increase of TGFBR1 as shown by qRT-PCR and immunoblot analysis. The increase was most pronounced when any 2 of the 3 cytokines (IFN-gamma, TNF-alpha, or IL-1-beta) were present.
Formal Description
Interaction-ID: 65796

gene/protein

Proinflammatory cytokine

increases_expression of

gene/protein

TGFBR1

in HUVEC cells
Drugbank entries Show/Hide entries for TGFBR1
Comment Induction of EndMT (endothelial to mesenchymal transition) by inflammatory cytokines in ECs (endothelial cells) in vitro resulted in a marked upregulation of mesenchymal markers (ZEB2, SLUG, SNAIL as shown by qRT-PCR, vimentin and collagen 1, shown by immunoblot analysis).
Formal Description
Interaction-ID: 65798

gene/protein

Proinflammatory cytokine

increases_expression of

gene/protein

ZEB2

in HUVEC cells
Comment Induction of EndMT (endothelial to mesenchymal transition) by inflammatory cytokines in ECs (endothelial cells) in vitro resulted in a marked upregulation of mesenchymal markers ZEB2, SLUG (SNAI2), SNAIL as shown by qRT-PCR, vimentin and collagen 1, shown by immunoblot analysis.
Formal Description
Interaction-ID: 65832

gene/protein

Proinflammatory cytokine

increases_expression of

gene/protein

SNAI2

in HUVEC cells
Comment Induction of EndMT (endothelial to mesenchymal transition) by inflammatory cytokines in ECs (endothelial cells) in vitro resulted in a marked upregulation of mesenchymal markers ZEB2, SLUG (SNAI2), SNAIL as shown by qRT-PCR, vimentin and collagen 1, shown by immunoblot analysis.
Formal Description
Interaction-ID: 65833

gene/protein

Proinflammatory cytokine

increases_expression of

gene/protein

SNAI1

in HUVEC cells
Comment Induction of EndMT (endothelial to mesenchymal transition) by inflammatory cytokines in ECs (endothelial cells) in vitro resulted in a marked upregulation of mesenchymal markers ZEB2, SLUG (SNAI2), SNAIL as shown by qRT-PCR, vimentin and collagen 1, shown by immunoblot analysis.
Formal Description
Interaction-ID: 65835

gene/protein

Proinflammatory cytokine

increases_quantity of

gene/protein

VIM

in HUVEC cells
Comment Induction of EndMT (endothelial to mesenchymal transition) by inflammatory cytokines in ECs (endothelial cells) in vitro resulted in a marked upregulation of mesenchymal markers ZEB2, SLUG (SNAI2), SNAIL as shown by qRT-PCR, vimentin and collagen 1, shown by immunoblot analysis.
Formal Description
Interaction-ID: 65836

gene/protein

Proinflammatory cytokine

increases_quantity of

gene/protein

COL1A1

in HUVEC cells
Drugbank entries Show/Hide entries for COL1A1
Comment Induction of EndMT (endothelial to mesenchymal transition) by inflammatory cytokines in ECs (endothelial cells) in vitro resulted in a marked upregulation of smooth muscle marker SM22-alpha (TAGLN) as shown shown by immunoblot analysis.
Formal Description
Interaction-ID: 65838

gene/protein

Proinflammatory cytokine

increases_quantity of

gene/protein

TAGLN

in HUVEC cells
Comment Induction of EndMT (endothelial to mesenchymal transition) by inflammatory cytokines in ECs (endothelial cells) in vitro resulted in a marked upregulation of leukocyte adhesion molecules (ICAM-1 and VCAM-1) as shown by qRT-PCR and immunoblot analysis.
Formal Description
Interaction-ID: 65840

gene/protein

Proinflammatory cytokine

increases_quantity of

gene/protein

ICAM1

in HUVEC cells
Drugbank entries Show/Hide entries for ICAM1
Comment Induction of EndMT (endothelial to mesenchymal transition) by inflammatory cytokines in ECs (endothelial cells) in vitro resulted in a marked upregulation of leukocyte adhesion molecules (ICAM-1 and VCAM-1) as shown by qRT-PCR and immunoblot analysis.
Formal Description
Interaction-ID: 65841

gene/protein

Proinflammatory cytokine

increases_expression of

gene/protein

ICAM1

in HUVEC cells
Drugbank entries Show/Hide entries for ICAM1
Comment Induction of EndMT (endothelial to mesenchymal transition) by inflammatory cytokines in ECs (endothelial cells) in vitro resulted in a marked upregulation of leukocyte adhesion molecules (ICAM-1 and VCAM-1) as shown by qRT-PCR and immunoblot analysis.
Formal Description
Interaction-ID: 65842

gene/protein

Proinflammatory cytokine

increases_quantity of

gene/protein

VCAM1

in HUVEC cells
Drugbank entries Show/Hide entries for VCAM1
Comment Induction of EndMT (endothelial to mesenchymal transition) by inflammatory cytokines in ECs (endothelial cells) in vitro resulted in a marked upregulation of leukocyte adhesion molecules (ICAM-1 and VCAM-1) as shown by qRT-PCR and immunoblot analysis.
Formal Description
Interaction-ID: 65843

gene/protein

Proinflammatory cytokine

increases_expression of

gene/protein

VCAM1

in HUVEC cells
Drugbank entries Show/Hide entries for VCAM1
Comment Induction of EndMT (endothelial to mesenchymal transition) by inflammatory cytokines in ECs (endothelial cells) in vitro resulted in a marked upregulation of monocyte chemotactic protein 1 (MCP-1 (CCL2)) as shown by qRT-PCR.
Formal Description
Interaction-ID: 65844

gene/protein

Proinflammatory cytokine

increases_expression of

gene/protein

CCL2

in HUVEC cells
Drugbank entries Show/Hide entries for CCL2
Comment Induction of EndMT (endothelial to mesenchymal transition) by inflammatory cytokines in ECs (endothelial cells) in vitro resulted in a marked upregulation of proinflammatory protein plasminogen activator inhibitor-1 (PAI-1 (SERPINE1)) as shown by qRT-PCR and immunoblot analysis.
Formal Description
Interaction-ID: 65845

gene/protein

Proinflammatory cytokine

increases_quantity of

gene/protein

SERPINE1

in HUVEC cells
Drugbank entries Show/Hide entries for SERPINE1
Comment Induction of EndMT (endothelial to mesenchymal transition) by inflammatory cytokines in ECs (endothelial cells) in vitro resulted in a marked upregulation of proinflammatory protein plasminogen activator inhibitor-1 (PAI-1 (SERPINE1)) as shown by qRT-PCR and immunoblot analysis.
Formal Description
Interaction-ID: 65846

gene/protein

Proinflammatory cytokine

increases_expression of

gene/protein

SERPINE1

in HUVEC cells
Drugbank entries Show/Hide entries for SERPINE1
Comment Induction of EndMT (endothelial to mesenchymal transition) by inflammatory cytokines in ECs (endothelial cells) in vitro resulted in the loss of protective protein endothelial NOS (eNOS (NOS3)) as shown by qRT-PCR and immunoblot analysis.
Formal Description
Interaction-ID: 65847

gene/protein

Proinflammatory cytokine

decreases_expression of

gene/protein

NOS3

in HUVEC cells
Drugbank entries Show/Hide entries for NOS3
Comment Induction of EndMT (endothelial to mesenchymal transition) by inflammatory cytokines in ECs (endothelial cells) in vitro resulted in the loss of protective protein endothelial NOS (eNOS (NOS3)) as shown by qRT-PCR and immunoblot analysis.
Formal Description
Interaction-ID: 65849

gene/protein

Proinflammatory cytokine

decreases_quantity of

gene/protein

NOS3

in HUVEC cells
Drugbank entries Show/Hide entries for NOS3
Comment Induction of EndMT (endothelial to mesenchymal transition) by inflammatory cytokines in ECs (endothelial cells) in vitro resulted in an increase of TGFBR1 as shown by qRT-PCR and immunoblot analysis. The increase was most pronounced when any 2 of the 3 cytokines (IFN-gamma, TNF-alpha, or IL-1-beta) were present.
Formal Description
Interaction-ID: 65853

gene/protein

Proinflammatory cytokine

increases_quantity of

gene/protein

TGFBR1

in HUVEC cells
Drugbank entries Show/Hide entries for TGFBR1
Comment HUVECs (human umbilical vein endothelial cells), treated with increasing concentrations of the cytokines IFN-gamma, TNF-alpha, or IL-1-beta showed a decrease in FGFR1 expression and an increase in EndMT markers. The reduction in FGFR1 expression was most pronounced when IFN-gamma, TNF-alpha, and IL-1-beta were used together. The decrease of FGFR1 has been shown by qRT-PCR and immunoblot analysis.
Formal Description
Interaction-ID: 65855

gene/protein

Proinflammatory cytokine

decreases_quantity of

gene/protein

FGFR1

in HUVEC cells
Drugbank entries Show/Hide entries for FGFR1
Comment None of the cytokines IFN-gamma, TNF-alpha, or IL-1-beta alone induced a reduction in expression of endothelial markers, such as vascular endothelial– cadherin (VE-cadherin (CDH5)) or VEGFR2. However, cytokine combinations profoundly reduced expression of these proteins.
Formal Description
Interaction-ID: 65858

gene/protein

Proinflammatory cytokine

decreases_quantity of

gene/protein

CDH5

in HUVEC cells; only combinations of cytokines are effective
Drugbank entries Show/Hide entries for CDH5
Comment None of the cytokines IFN-gamma, TNF-alpha, or IL-1-beta alone induced a reduction in expression of endothelial markers, such as vascular endothelial– cadherin (VE-cadherin (CDH5)) or VEGFR2 (KDR). However, cytokine combinations profoundly reduced expression of these proteins.
Formal Description
Interaction-ID: 65859

gene/protein

Proinflammatory cytokine

decreases_quantity of

gene/protein

KDR

in HUVEC cells; only combinations of cytokines are effective
Drugbank entries Show/Hide entries for KDR
Comment Induction of EndMT (endothelial to mesenchymal transition) by inflammatory cytokines in ECs (endothelial cells) in vitro resulted in an upregulation of N-cadherin (CDH2) as shown by qRT-PCR and immunoblot analysis. Cytokine combinations profoundly increased expression of these protein.
Formal Description
Interaction-ID: 65860

gene/protein

Proinflammatory cytokine

increases_expression of

gene/protein

CDH2

in HUVEC cells; combinations of cytokines are more effective
Comment Induction of EndMT (endothelial to mesenchymal transition) by inflammatory cytokines in ECs (endothelial cells) in vitro resulted in an upregulation of N-cadherin (CDH2) as shown by qRT-PCR and immunoblot analysis. Cytokine combinations profoundly increased expression of these protein.
Formal Description
Interaction-ID: 65862

gene/protein

Proinflammatory cytokine

increases_quantity of

gene/protein

CDH2

in HUVEC cells; combinations of cytokines are more effective
Comment None of the cytokines IFN-gamma, TNF-alpha, or IL-1-beta alone induced a reduction in expression of endothelial markers, such as vascular endothelial– cadherin (VE-cadherin (CDH5)) or VEGFR2 (KDR). However, cytokine combinations profoundly reduced expression of these proteins.
Formal Description
Interaction-ID: 128943

gene/protein

Proinflammatory cytokine

decreases_quantity of

gene/protein

KDR

in HUVEC cells; only combinations of cytokines are effective
Drugbank entries Show/Hide entries for KDR